Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer
Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer
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DOI：
10.1002/em.20000
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发表时间：
2004-01-01
影响因子：
2.8
通讯作者：
Strange, RC
中科院分区：
文献类型：
--
作者：
Bodiwala, D;Luscombe, CJ;Strange, RC
紫外线辐射（UVR）暴露可能通过涉及维生素D的机制防止前列腺癌的发展。因此，维生素D受体（VDR）基因是前列腺癌的候选易感因素。这种可能性以前已经研究过，结果相互矛盾。我们通过研究368例前列腺癌和243例良性前列腺肥大（BPH）患者，研究了VDR基因型（CDX-2、Fok 1和Taq 1位点的变异）、单倍型和基因型组合与风险的关系。CDX-2、Fok 1和Taq 1基因型和单倍型频率在癌症和BPH患者中没有显著差异。由于VDR多态性的影响可能取决于UVR暴露，因此我们研究了将男性分层为低（低于中位数）和高（高于中位数）累积暴露/年组的变异与风险的相关性。在UVR暴露高于中位数（1，100小时/年）的男性中，CDX-2 GA和AA（比值比[OR]分别为2.11和2.02）和Fok 1 ff（OR 2.91）与前列腺癌风险增加相关。Taq 1基因型没有观察到相关性。在基因型组合中，相对于所有其他CDX-2和Taq 1及其组合，GGTT（P = 0.022，OR = 0.30），以及相对于所有其他Fok 1和Taq 1组合，FFTT（P = 0.026，OR = 0.35）与存在主效应的前列腺癌风险降低相关。其他两种或三种基因型组合均与风险无关。这些数据表明，VDR变异影响前列腺癌的风险，这种关联取决于UVR暴露的程度。(C)2004 Wiley-Liss，Inc.
Ultraviolet radiation (UVR) exposure may protect against prostate cancer development via a mechanism involving vitamin D. The vitamin D receptor (VDR) gene is therefore a candidate susceptibility factor for prostate cancer. This possibility has been previously investigated with conflicting results. We examined the association of VDR genotypes (variants at the CDX-2, Fok1, and Taq1 sites), haplotypes, and genotype combinations with risk by studying 368 prostate cancer and 243 benign prostatic hypertrophy (BPH) patients. CDX-2, Fok1, and Taq1 genotype and haplotype frequencies were not significantly different in cancer and BPH patients. As the impact of VDR polymorphisms may depend on UVR exposure, we studied associations of variants with risk in men stratified into low (below median) and high (above median) cumulative exposure/year groups. In men with UVR exposure above the median (1,100 hr/year), CDX-2 GA and AA (odds ratios [OR] 2.11 and 2.02, respectively) and Fok1 ff (OR 2.91) were associated with increased prostate cancer risk. No associations were observed for Taq1 genotypes. Of the genotype combinations, relative to all other CDX-2 and Taq1 and combinations, GGTT (P = 0.022, OR = 0.30), and relative to all other Fok1 and Taq1 combinations, FFTT (P = 0.026, OR = 0.35) were associated with reduced prostate cancer risk in the presence of the main effects. None of the other two- or three-genotype combinations was associated with risk. These data indicate that VDR variants influence prostate cancer risk and that this association is dependent on the extent of UVR exposure. (C) 2004 Wiley-Liss, Inc.